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Assessment of PTEN tumor suppressor activity in nonmammalian models: the year of the yeast

Abstract

Model organisms have emerged as suitable and reliable biological tools to study the properties of proteins whose function is altered in human disease. In the case of the PI3K and PTEN human cancer-related proteins, several vertebrate and invertebrate models, including mouse, fly, worm and amoeba, have been exploited to obtain relevant functional information that has been conserved from these organisms to humans along evolution. The yeast Saccharomyces cerevisiae is an eukaryotic unicellular organism that lacks a canonical mammalian-like PI3K/PTEN pathway and PIP3 as a physiological second messenger, PIP2 being essential for its life. The mammalian PI3K/PTEN pathway can be reconstituted in S. cerevisiae, generating growth alteration phenotypes that can be easily monitored to perform in vivo functional analysis of the molecular constituents of this pathway. Here, we review the current nonmammalian model systems to study PTEN function, summarize our knowledge of PTEN orthologs in yeast species and propose the yeast S. cerevisiae as a sensitive biological sensor of PI3K oncogenicity and PTEN tumor suppressor activity.

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References

  • Andrés-Pons A, Rodríguez-Escudero I, Gil A, Blanco A, Vega A, Molina M et al. (2007). In vivo functional analysis of the counterbalance of hyperactive phosphatidylinositol 3-kinase p110 catalytic oncoproteins by the tumor suppressor PTEN. Cancer Res 67: 9731–9739.

    Article  PubMed  CAS  Google Scholar 

  • Beeton CA, Chance EM, Foukas LC, Shepherd PR . (2000). Comparison of the kinetic properties of the lipid- and protein-kinase activities of the p110alpha and p110beta catalytic subunits of class-Ia phosphoinositide 3-kinases. Biochem J 350: 353–359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K et al. (2007). A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12: 395–402.

    Article  CAS  PubMed  Google Scholar 

  • Bhaskar PT, Hay N . (2007). The two TORCs and Akt. Dev Cell 12: 487–502.

    Article  CAS  PubMed  Google Scholar 

  • Casamayor A, Torrance PD, Kobayashi T, Thorner J, Alessi DR . (1999). Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. Curr Biol 9: 186–197.

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Iijima M, Tang M, Landree MA, Huang YE, Xiong Y et al. (2007). PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis. Dev Cell 12: 603–614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chow LM, Baker SJ . (2006). PTEN function in normal and neoplastic growth. Cancer Lett 241: 184–196.

    Article  CAS  PubMed  Google Scholar 

  • Croushore J, Blasiole B, Riddle RC, Thisse C, Thisse B, Canfield VA et al. (2005). ptena and ptenb genes play distinct roles in zebrafish embryogenesis. Dev Dyn 234: 911–921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fabrizio P, Pozza F, Pletcher SD, Gendron CM, Longo VD . (2001). Regulation of longevity and stress resistance by Sch9 in yeast. Science 292: 288–290.

    Article  CAS  PubMed  Google Scholar 

  • Faucherre A, Taylor GS, Overvoorde J, Dixon JE, Hertog J . (2008). Zebrafish pten genes have overlapping and non-redundant functions in tumorigenesis and embryonic development. Oncogene 27: 1079–1086.

    Article  CAS  PubMed  Google Scholar 

  • Fox JA, Ung K, Tanlimco SG, Jirik FR . (2002). Disruption of a single Pten allele augments the chemotactic response of B lymphocytes to stromal cell-derived factor-1. J Immunol 169: 49–54.

    Article  CAS  PubMed  Google Scholar 

  • Frattini M, Saletti P, Romagnani E, Martin V, Molinari F, Ghisletta M et al. (2007). PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer 97: 1139–1145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friant S, Lombardi R, Schmelzle T, Hall MN, Riezman H . (2001). Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast. EMBO J 20: 6783–6792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukuyama M, Rougvie AE, Rothman JH . (2006). C. elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and growth in the germline. Curr Biol 16: 773–779.

    Article  CAS  PubMed  Google Scholar 

  • Funaki M, Katagiri H, Kanda A, Anai M, Nawano M, Ogihara T et al. (1999). p85/p110-type phosphatidylinositol kinase phosphorylates not only the D-3, but also the D-4 position of the inositol ring. J Biol Chem 274: 22019–22024.

    Article  CAS  PubMed  Google Scholar 

  • Funamoto S, Meili R, Lee S, Parry L, Firtel RA . (2002). Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell 109: 611–623.

    Article  CAS  PubMed  Google Scholar 

  • Gao P, Wange RL, Zhang N, Oppenheim JJ, Howard OM . (2005). Negative regulation of CXCR4-mediated chemotaxis by the lipid phosphatase activity of tumor suppressor PTEN. Blood 106: 2619–2626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao X, Neufeld TP, Pan D . (2000). Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways. Dev Biol 221: 404–418.

    Article  CAS  PubMed  Google Scholar 

  • Georgescu MM, Kirsch KH, Akagi T, Shishido T, Hanafusa H . (1999). The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region. Proc Natl Acad Sci USA 96: 10182–10187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Georgescu MM, Kirsch KH, Kaloudis P, Yang H, Pavletich NP, Hanafusa H . (2000). Stabilization and productive positioning roles of the C2 domain of PTEN tumor suppressor. Cancer Res 60: 7033–7038.

    CAS  PubMed  Google Scholar 

  • Gil EB, Malone Link E, Liu LX, Johnson CD, Lees JA . (1999). Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene. Proc Natl Acad Sci USA 96: 2925–2930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goberdhan DC, Paricio N, Goodman EC, Mlodzik M, Wilson C . (1999). Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes Dev 13: 3244–3258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grunwald V, DeGraffenried L, Russel D, Friedrichs W, Ray RB, Hidalgo M . (2002). Inhibitors of mTOR reverse doxorubicin resistance conferred by PTEN status in prostate cancer cells. Cancer Res 62: 6141–6145.

    CAS  PubMed  Google Scholar 

  • Gupta R, Ting JT, Sokolov LN, Johnson SA, Luan S . (2002). A tumor suppressor homolog, AtPTEN1, is essential for pollen development in Arabidopsis. Plant Cell 14: 2495–2507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han SY, Kato H, Kato S, Suzuki T, Shibata H, Ishii S et al. (2000). Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay. Cancer Res 60: 3147–3151.

    CAS  PubMed  Google Scholar 

  • Hanada M, Feng J, Hemmings BA . (2004). Structure, regulation and function of PKB/AKT-a major therapeutic target. Biochim Biophys Acta 1697: 3–16.

    Article  CAS  PubMed  Google Scholar 

  • Hariharan IK, Bilder D . (2006). Regulation of imaginal disc growth by tumor-suppressor genes in Drosophila. Annu Rev Genet 40: 335–361.

    Article  CAS  PubMed  Google Scholar 

  • Heymont J, Berenfeld L, Collins J, Kaganovich A, Maynes B, Moulin A et al. (2000). TEP1, the yeast homolog of the human tumor suppressor gene PTEN/MMAC1/TEP1, is linked to the phosphatidylinositol pathway and plays a role in the developmental process of sporulation. Proc Natl Acad Sci USA 97: 12672–12677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoeller O, Kay RR . (2007). Chemotaxis in the absence of PIP3 gradients. Curr Biol 17: 813–817.

    Article  CAS  PubMed  Google Scholar 

  • Huang H, Potter CJ, Tao W, Li DM, Brogiolo W, Hafen E et al. (1999). PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development 126: 5365–5372.

    Article  CAS  PubMed  Google Scholar 

  • Humphrey JS, Salim A, Erdos MR, Collins FS, Brody LC, Klausner RD . (1997). Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing. Proc Natl Acad Sci USA 94: 5820–5825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iijima M, Devreotes P . (2002). Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109: 599–610.

    Article  CAS  PubMed  Google Scholar 

  • Iijima M, Huang YE, Luo HR, Vazquez F, Devreotes PN . (2004). Novel mechanism of PTEN regulation by its phosphatidylinositol 4,5-bisphosphate binding motif is critical for chemotaxis. J Biol Chem 279: 16606–16613.

    Article  CAS  PubMed  Google Scholar 

  • Inagaki M, Schmelzle T, Yamaguchi K, Irie K, Hall MN, Matsumoto K . (1999). PDK1 homologs activate the Pkc1-mitogen-activated protein kinase pathway in yeast. Mol Cell Biol 19: 8344–8352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Isakoff SJ, Cardozo T, Andreev J, Li Z, Ferguson KM, Abagyan R et al. (1998). Identification and analysis of PH domain-containing targets of phosphatidylinositol 3-kinase using a novel in vivo assay in yeast. EMBO J 17: 5374–5387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishioka C, Frebourg T, Yan YX, Vidal M, Friend SH, Schmidt S et al. (1993). Screening patients for heterozygous p53 mutations using a functional assay in yeast. Nat Genet 5: 124–129.

    Article  CAS  PubMed  Google Scholar 

  • Jiang Z, Pore N, Cerniglia GJ, Mick R, Georgescu MM, Bernhard EJ et al. (2007). Phosphatase and tensin homologue deficiency in glioblastoma confers resistance to radiation and temozolomide that is reversed by the protease inhibitor nelfinavir. Cancer Res 67: 4467–4473.

    Article  CAS  PubMed  Google Scholar 

  • Kaeberlein M, Powers III RW, Steffen KK, Westman EA, Hu D, Dang N et al. (2005). Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310: 1193–1196.

    Article  CAS  PubMed  Google Scholar 

  • Karakas B, Bachman KE, Park BH . (2006). Mutation of the PIK3CA oncogene in human cancers. Br J Cancer 94: 455–459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato H, Kato S, Kumabe T, Sonoda Y, Yoshimoto T, Han S et al. (2000). Functional evaluation of p53 and PTEN gene mutations in gliomas. Clin Cancer Res 6: 3937–3943.

    CAS  PubMed  Google Scholar 

  • Kishimoto H, Hamada K, Saunders M, Backman S, Sasaki T, Nakano T et al. (2003). Physiological functions of Pten in mouse tissues. Cell Struct Funct 28: 11–21.

    Article  CAS  PubMed  Google Scholar 

  • Kunz J, Henriquez R, Schneider U, Deuter-Reinhard M, Movva NR, Hall MN . (1993). Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73: 585–596.

    Article  CAS  PubMed  Google Scholar 

  • Lacalle RA, Gómez-Moutón C, Barber DF, Jiménez-Baranda S, Mira E, Martínez AC et al. (2004). PTEN regulates motility but not directionality during leukocyte chemotaxis. J Cell Sci 117: 6207–6215.

    Article  CAS  PubMed  Google Scholar 

  • Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y et al. (1999). Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell 99: 323–334.

    Article  CAS  PubMed  Google Scholar 

  • Li L, Ernsting BR, Wishart MJ, Lohse DL, Dixon JE . (1997). A family of putative tumor suppressors is structurally and functionally conserved in humans and yeast. J Biol Chem 272: 29403–29406.

    Article  CAS  PubMed  Google Scholar 

  • Liu K, Zhang X, Lester RL, Dickson RC . (2005a). The sphingoid long chain base phytosphingosine activates AGC-type protein kinases in Saccharomyces cerevisiae including Ypk1, Ypk2, and Sch9. J Biol Chem 280: 22679–22687.

    Article  CAS  PubMed  Google Scholar 

  • Liu K, Zhang X, Sumanasekera C, Lester RL, Dickson RC . (2005b). Signalling functions for sphingolipid long-chain bases in Saccharomyces cerevisiae. Biochem Soc Trans 33: 1170–1173.

    Article  CAS  PubMed  Google Scholar 

  • Lopiccolo J, Blumenthal GM, Bernstein WB, Dennis PA . (2008). Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updat 11: 32–50.

    Article  CAS  PubMed  Google Scholar 

  • Lorenz MC, Heitman J . (1995). TOR mutations confer rapamycin resistance by preventing interaction with FKBP12-rapamycin. J Biol Chem 270: 27531–27537.

    Article  CAS  PubMed  Google Scholar 

  • Maehama T, Kosaka N, Okahara F, Takeuchi K, Umeda M, Dixon JE et al. (2004). Suppression of a phosphatidylinositol 3-kinase signal by a specific spliced variant of Drosophila PTEN. FEBS Lett 565: 43–47.

    Article  CAS  PubMed  Google Scholar 

  • Maehama T, Taylor GS, Dixon JE . (2001). PTEN and myotubularin: novel phosphoinositide phosphatases. Annu Rev Biochem 70: 247–279.

    Article  CAS  PubMed  Google Scholar 

  • Mager WH, Winderickx J . (2005). Yeast as a model for medical and medicinal research. Trends Pharmacol Sci 26: 265–273.

    Article  CAS  PubMed  Google Scholar 

  • Marone R, Cmiljanovic V, Giese B, Wymann MP . (2008). Targeting phosphoinositide 3-kinase: moving towards therapy. Biochim Biophys Acta 1784: 159–185.

    Article  CAS  PubMed  Google Scholar 

  • Masse I, Molin L, Billaud M, Solari F . (2005). Lifespan and dauer regulation by tissue-specific activities of Caenorhabditis elegans DAF-18. Dev Biol 286: 91–101.

    Article  CAS  PubMed  Google Scholar 

  • Matsuo T, Kubo Y, Watanabe Y, Yamamoto M . (2003). Schizosaccharomyces pombe AGC family kinase Gad8p forms a conserved signaling module with TOR and PDK1-like kinases. EMBO J 22: 3073–3083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melese T, Hieter P . (2002). From genetics and genomics to drug discovery: yeast rises to the challenge. Trends Pharmacol Sci 23: 544–547.

    Article  CAS  PubMed  Google Scholar 

  • Mihaylova VT, Borland CZ, Manjarrez L, Stern MJ, Sun H . (1999). The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway. Proc Natl Acad Sci USA 96: 7427–7432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mitra P, Zhang Y, Rameh LE, Ivshina MP, McCollum D, Nunnari JJ et al. (2004). A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast. J Cell Biol 166: 205–211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA et al. (2004). PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6: 117–127.

    Article  CAS  PubMed  Google Scholar 

  • Niederberger C, Schweingruber ME . (1999). A Schizosaccharomyces pombe gene, ksg1, that shows structural homology to the human phosphoinositide-dependent protein kinase PDK1, is essential for growth, mating and sporulation. Mol Gen Genet 261: 177–183.

    Article  CAS  PubMed  Google Scholar 

  • Nishio M, Watanabe K, Sasaki J, Taya C, Takasuga S, Iizuka R et al. (2007). Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1. Nat Cell Biol 9: 36–44.

    Article  CAS  PubMed  Google Scholar 

  • Ogg S, Ruvkun G . (1998). The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol Cell 2: 887–893.

    Article  CAS  PubMed  Google Scholar 

  • Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M et al. (2007). Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med 13: 1203–1210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pascual-Ahuir A, Proft M . (2007). Control of stress-regulated gene expression and longevity by the Sch9 protein kinase. Cell Cycle 6: 2445–2447.

    Article  CAS  PubMed  Google Scholar 

  • Pedruzzi I, Dubouloz F, Cameroni E, Wanke V, Roosen J, Winderickx J et al. (2003). TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0. Mol Cell 12: 1607–1613.

    Article  CAS  PubMed  Google Scholar 

  • Pinal N, Goberdhan DC, Collinson L, Fujita Y, Cox IM, Wilson C et al. (2006). Regulated and polarized PtdIns(3,4,5)P3 accumulation is essential for apical membrane morphogenesis in photoreceptor epithelial cells. Curr Biol 16: 140–149.

    Article  CAS  PubMed  Google Scholar 

  • Pulido R, van Huijsduijnen RH . (2008). Protein tyrosine phosphatases: dual-specificity phosphatases in health and disease. FEBS J 275: 848–866.

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez-Escudero I, Roelants FM, Thorner J, Nombela C, Molina M, Cid VJ . (2005). Reconstitution of the mammalian PI3K/PTEN/Akt pathway in yeast. Biochem J 390: 613–623.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Roelants FM, Torrance PD, Bezman N, Thorner J . (2002). Pkh1 and pkh2 differentially phosphorylate and activate ypk1 and ykr2 and define protein kinase modules required for maintenance of cell wall integrity. Mol Biol Cell 13: 3005–3028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roosen J, Engelen K, Marchal K, Mathys J, Griffioen G, Cameroni E et al. (2005). PKA and Sch9 control a molecular switch important for the proper adaptation to nutrient availability. Mol Microbiol 55: 862–880.

    Article  CAS  PubMed  Google Scholar 

  • Rouault JP, Kuwabara PE, Sinilnikova OM, Duret L, Thierry-Mieg D, Billaud M . (1999). Regulation of dauer larva development in Caenorhabditis elegans by daf-18, a homologue of the tumour suppressor PTEN. Curr Biol 9: 329–332.

    Article  CAS  PubMed  Google Scholar 

  • Roux AE, Quissac A, Chartrand P, Ferbeyre G, Rokeach LA . (2006). Regulation of chronological aging in Schizosaccharomyces pombe by the protein kinases Pka1 and Sck2. Aging Cell 5: 345–357.

    Article  CAS  PubMed  Google Scholar 

  • Scanga SE, Ruel L, Binari RC, Snow B, Stambolic V, Bouchard D et al. (2000). The conserved PI3′K/PTEN/Akt signaling pathway regulates both cell size and survival in Drosophila. Oncogene 19: 3971–3977.

    Article  CAS  PubMed  Google Scholar 

  • Sharrard RM, Maitland NJ . (2000). Alternative splicing of the human PTEN/MMAC1/TEP1 gene. Biochim Biophys Acta 1494: 282–285.

    Article  CAS  PubMed  Google Scholar 

  • Shimodaira H, Filosi N, Shibata H, Suzuki T, Radice P, Kanamaru R et al. (1998). Functional analysis of human MLH1 mutations in Saccharomyces cerevisiae. Nat Genet 19: 384–389.

    Article  CAS  PubMed  Google Scholar 

  • Smith A, Alrubaie S, Coehlo C, Leevers SJ, Ashworth A . (1999). Alternative splicing of the Drosophila PTEN gene. Biochim Biophys Acta 1447: 313–317.

    Article  CAS  PubMed  Google Scholar 

  • Solari F, Bourbon-Piffaut A, Masse I, Payrastre B, Chan AM, Billaud M . (2005). The human tumour suppressor PTEN regulates longevity and dauer formation in Caenorhabditis elegans. Oncogene 24: 20–27.

    Article  CAS  PubMed  Google Scholar 

  • Song Z, Saghafi N, Gokhale V, Brabant M, Meuillet EJ . (2007). Regulation of the activity of the tumor suppressor PTEN by thioredoxin in Drosophila melanogaster. Exp Cell Res 313: 1161–1171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steelman LS, Navolanic PM, Sokolosky ML, Taylor JR, Lehmann BD, Chappell WH et al. (2008). Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors. Oncogene 27: 4086–4095.

    Article  CAS  PubMed  Google Scholar 

  • Stocker H, Andjelkovic M, Oldham S, Laffargue M, Wymann MP, Hemmings BA et al. (2002). Living with lethal PIP3 levels: viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB. Science 295: 2088–2091.

    Article  CAS  PubMed  Google Scholar 

  • Strahl T, Thorner J . (2007). Synthesis and function of membrane phosphoinositides in budding yeast, Saccharomyces cerevisiae. Biochim Biophys Acta 1771: 353–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Subramanian KK, Jia Y, Zhu D, Simms BT, Jo H, Hattori H et al. (2007). Tumor suppressor PTEN is a physiologic suppressor of chemoattractant-mediated neutrophil functions. Blood 109: 4028–4037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun Y, Taniguchi R, Tanoue D, Yamaji T, Takematsu H, Mori K et al. (2000). Sli2 (Ypk1), a homologue of mammalian protein kinase SGK, is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. Mol Cell Biol 20: 4411–4419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki A, Nakano T, Mak TW, Sasaki T . (2008). Portrait of PTEN: messages from mutant mice. Cancer Sci 99: 209–213.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki T, Ishioka C, Kato S, Mitachi Y, Shimodaira H, Sakayori M et al. (1998). Detection of APC mutations by a yeast-based protein truncation test (YPTT). Genes Chromosomes Cancer 21: 290–297.

    Article  CAS  PubMed  Google Scholar 

  • Tamguney T, Stokoe D . (2007). New insights into PTEN. J Cell Sci 120: 4071–4079.

    Article  CAS  PubMed  Google Scholar 

  • Tugendreich S, Perkins E, Couto J, Barthmaier P, Sun D, Tang S et al. (2001). A streamlined process to phenotypically profile heterologous cDNAs in parallel using yeast cell-based assays. Genome Res 11: 1899–1912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ueno S, Kono R, Iwao Y . (2006). PTEN is required for the normal progression of gastrulation by repressing cell proliferation after MBT in Xenopus embryos. Dev Biol 297: 274–283.

    Article  CAS  PubMed  Google Scholar 

  • Urban J, Soulard A, Huber A, Lippman S, Mukhopadhyay D, Deloche O et al. (2007). Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Mol Cell 26: 663–674.

    Article  CAS  PubMed  Google Scholar 

  • Valiente M, Andrés-Pons A, Gomar B, Torres J, Gil A, Tapparel C et al. (2005). Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases. J Biol Chem 280: 28936–28943.

    Article  CAS  PubMed  Google Scholar 

  • Vogt PK, Kang S, Elsliger MA, Gymnopoulos M . (2007). Cancer-specific mutations in phosphatidylinositol 3-kinase. Trends Biochem Sci 32: 342–349.

    Article  CAS  PubMed  Google Scholar 

  • von Stein W, Ramrath A, Grimm A, Muller-Borg M, Wodarz A . (2005). Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling. Development 132: 1675–1686.

    Article  CAS  PubMed  Google Scholar 

  • Walther TC, Aguilar PS, Frohlich F, Chu F, Moreira K, Burlingame AL et al. (2007). Pkh-kinases control eisosome assembly and organization. EMBO J 26: 4946–4955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wan W, Zou H, Sun R, Liu Y, Wang J, Ma D et al. (2007). Investigate the role of PTEN in chemotaxis of human breast cancer cells. Cell Signal 19: 2227–2236.

    Article  CAS  PubMed  Google Scholar 

  • Wessels D, Lusche DF, Kuhl S, Heid P, Soll DR . (2007). PTEN plays a role in the suppression of lateral pseudopod formation during Dictyostelium motility and chemotaxis. J Cell Sci 120: 2517–2531.

    Article  CAS  PubMed  Google Scholar 

  • Wu H, Feng W, Chen J, Chan LN, Huang S, Zhang M . (2007). PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Mol Cell 28: 86–898.

    Article  CAS  Google Scholar 

  • Wu X, Hepner K, Castelino-Prabhu S, Do D, Kaye MB, Yuan XJ et al. (2000a). Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. Proc Natl Acad Sci USA 97: 4233–4238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu Y, Dowbenko D, Spencer S, Laura R, Lee J, Gu Q et al. (2000b). Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase. J Biol Chem 275: 21477–21485.

    Article  CAS  PubMed  Google Scholar 

  • Yu JW, Mendrola JM, Audhya A, Singh S, Keleti D, DeWald DB et al. (2004). Genome-wide analysis of membrane targeting by S.cerevisiae pleckstrin homology domains. Mol Cell 13: 677–688.

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Loijens JC, Boronenkov IV, Parker GJ, Norris FA, Chen J et al. (1997). Phosphatidylinositol-4-phosphate 5-kinase isozymes catalyze the synthesis of 3-phosphate-containing phosphatidylinositol signaling molecules. J Biol Chem 272: 17756–17761.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank T Maehama (National Institute of Infectious Diseases, Tokyo, Japan) and E Hidalgo (Universitat Pompeu Fabra, Barcelona, Spain) for providing DNA samples. Work at the authors' labs is supported by Grants SAF2006-083139 from Ministerio de Educación y Ciencia, and Grants ISCIII-RETIC RD06/0020 (to R Pulido) and CP04/00318 (to A Gil) from Instituto de Salud Carlos III, Spain-FEDER; European Research Training Network Grant MRTN-CT-2006-035830 (to R Pulido and J den Hertog); and Grants BIO2004-02019 from Ministerio de Educación y Ciencia, and S-SAL-0246-2006 from Comunidad Autónoma de Madrid, Spain (to M Molina). A Andrés-Pons and C Romá-Mateo have been the recipients of predoctoral fellowships from Ministerio de Educación y Ciencia and Ayuntamiento de Valencia, Spain.

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Cid, V., Rodríguez-Escudero, I., Andrés-Pons, A. et al. Assessment of PTEN tumor suppressor activity in nonmammalian models: the year of the yeast. Oncogene 27, 5431–5442 (2008). https://doi.org/10.1038/onc.2008.240

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